Shigella sonnei is a major causative organism of shigellosis worldwide, that appears the most prevalent of Shigellae in developed countries. We are developing synthetic oligosaccharide-based immunogens as possible vaccine candidates against this organism using an approach similar to the synthetic vaccine project targeting a conjugate vaccine against S. dysenteriae type 1. The O-SP of S. sonnei consists of a disaccharide repeating unit containing the unique sugars 2-acetamido-2-deoxy-l-altruronic acid and 2-acetamido-4-amino-2,4,6-trideoxy-d-galactose in a- and b-linked form, respectively. Using nuclear magnetic resonance spectroscopy we found that this polysaccharide has a zwitterionic structure with opposite charges at each consecutive residue. Starting from l-glucose and d-glucosamine, we synthesized the monosaccharide components of this polysaccharide the first time as their methyl glycosides in their natural anomeric configuration. NMR studies indicated that the trideoxy-galactose component exists in the 4C1 conformation whereas the conformations of the altruronic acid derivatives depend on their substitution pattern. The free uronic acid exists as an equilibrium mixture of the 4C1 and 1C4 chair conformers. We published complete assignments for the 1H and 13C NMR spectra of the O-SP and presented evidence that both pyranose residues in the polysaccharide exist in the 4C1 conformation. We have designed synthetic schemes for the assembly of the disaccharide repeating unit and for larger oligosaccharides of the O-SP of S. sonnei.
